1. Field of the Invention
The present invention relates generally to the fields of virology, immunology and pathology. More particularly, it concerns the development of monoclonal antibodies for use in the diagnosis, prevention and therapy of influenza virus infections, particular those of the H1N1 subtype.
2. Background of the Invention
Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae (the “influenza viruses”), that affects birds and mammals. The name influenza comes from the Italian influenza, meaning “influence” (Latin: influentia). The most common symptoms of the disease are chills, fever, pharyngitis, muscle pains, severe headache, coughing, weakness and general discomfort. Fever and coughs are the most frequent symptoms. In more serious cases, influenza causes pneumonia, which can be fatal, particularly for the young and the elderly. Although it is often confused with the common cold, influenza is a much more severe disease and is caused by a different type of virus. Influenza may produce nausea and vomiting, particularly in children, but these symptoms are more common in the unrelated disease gastroenteritis, which is sometimes called “stomach flu” or “24-hour flu.”
Typically, influenza is transmitted from infected mammals through the air by coughs or sneezes, creating aerosols containing the virus, and from infected birds through their droppings. Influenza can also be transmitted by saliva, nasal secretions, feces and blood. Infections also occur through contact with these body fluids or with contaminated surfaces. Flu viruses can remain infectious for about one week at human body temperature, over 30 days at 0° C. (32° F.), and for much longer periods at very low temperatures. Influenza viruses can be inactivated by disinfectants and detergents. As the virus can be inactivated by soap, frequent hand washing reduces the risk of infection.
The symptoms of human influenza were clearly described by Hippocrates roughly 2,400 years ago. Since then, the virus has caused numerous pandemics. Historical data on influenza are difficult to interpret, because the symptoms can be similar to those of other diseases, such as diphtheria, pneumonic plague, typhoid fever, dengue, or typhus. The first convincing record of an influenza pandemic was of an outbreak in 1580, which began in Russia and spread to Europe via Africa. In Rome, over 8,000 people were killed, and several Spanish cities were almost wiped out. Pandemics continued sporadically throughout the 17th and 18th centuries, with the pandemic of 1830-1833 being particularly widespread; it infected approximately a quarter of the people exposed. The most famous and lethal outbreak was the so-called Spanish flu pandemic (type A influenza, H1N1 subtype), which lasted from 1918 to 1919. It is not known exactly how many it killed, but estimates range from 20 to 100 million people. Later flu pandemics were not so devastating. They included the 1957 Asian Flu (type A, H2N2 strain) and the 1968 Hong Kong Flu (type A, H3N2 strain), but even these smaller outbreaks killed millions of people. In later pandemics, antibiotics were available to control secondary infections and this may have helped reduce mortality compared to the Spanish Flu of 1918. An avian strain named H5N1 has recently posed the greatest risk for a new influenza pandemic since it first killed humans in Asia in the 1990's. Each of these pandemics was caused by the appearance of a new strain of the virus in humans. Often, these new strains result from the spread of an existing flu virus to humans from other animal species.
Vaccinations against influenza are usually given to people in developed countries and to farmed poultry. The most common human vaccine is the trivalent influenza vaccine (TIV) that contains purified and inactivated material from three viral strains. Typically, this vaccine includes material from two influenza A virus subtypes and one influenza B virus strain. The TIV carries no risk of transmitting the disease, and it has very low reactivity. A vaccine formulated for one year may be ineffective in the following year, since the influenza virus evolves rapidly, and different strains become dominant. Antiviral drugs can be used to treat influenza, with neuraminidase inhibitors being particularly effective.
In April 2009, a novel H1N1 flu strain that combined genes from human, pig, and bird flu, initially dubbed the “swine flu,” emerged in Mexico, the United States, and several other nations. By late April, the H1N1 swine flu was suspected of having killed over 150 in Mexico, and prompted concern that a new pandemic is imminent. The structural similarity to the 1918 Spanish Flu, possibly the greatest medical disaster of all times, highlights to ongoing threat from influenza virus generally, and the H1N1 subtype in particular. Therefore, compositions and methods for the diagnosis, prevention and treatment of this disease remain highly sought after.